Th17 cells and ILC3s define a spectrum of psoriasis endotypes via the IL-23/IL-17 axis

Psoriasis is a chronic inflammatory skin disease characterized by keratinocyte hyperproliferation and immune cell infiltration. A central driver is the interleukin-23/interleukin-17 (IL-23/IL-17) axis, which promotes inflammation and epidermal hyperproliferation. Current treatments often target this axis broadly, but clinical responses vary, suggesting underlying immunological heterogeneity. Understanding the specific cellular contributions to this axis, particularly from adaptive T helper 17 (Th17) cells and innate group 3 innate lymphoid cells (ILC3s), is crucial for refining disease classification and developing precision therapies. This paper explores how the balance and plasticity between these two cell types contribute to distinct disease endotypes.

This conceptual paper synthesizes existing immunological evidence to propose a refined understanding of psoriasis pathogenesis. It analyzes the functional overlap and extensive crosstalk between adaptive T helper 17 (Th17) cells and innate group 3 innate lymphoid cells (ILC3s). The authors did not conduct a new experimental study but rather integrated current knowledge regarding the IL-23/IL-17 axis and its cellular drivers to elucidate how these populations contribute to disease heterogeneity and potential therapeutic responses.

The paper highlights that both Th17 cells and ILC3s are key drivers of the IL-23/IL-17 axis, sharing the ability to produce pro-inflammatory cytokines such as IL-17A, IL-17F, and IL-22. These cytokines activate keratinocytes, promoting epidermal hyperproliferation and sustaining the inflammatory microenvironment characteristic of psoriatic lesions. Th17 cells contribute to chronic inflammation through antigen-driven adaptive immune responses, while ILC3s provide an early, antigen-independent source of IL-17 and IL-22 in rapid response to cytokine signals like IL-23. > Increasing evidence suggests that psoriasis comprises immunological endotypes where either Th17 cells or ILC3s may predominate, leading to clinical heterogeneity and differential responses to targeted therapies. This functional overlap and extensive crosstalk between Th17 cells and ILC3s create a robust and self-amplifying inflammatory circuit, making psoriasis a valuable model for understanding immune regulation in chronic inflammatory and autoimmune diseases.